general characteristics
The main non-collagenous protein of bone and dental tissue. Synthesized by osteoblasts and odontoblasts, it reflects the metabolic activity of bone tissue osteoblasts. The synthesis of osteocalcin is directly influenced by calcitonin and parathyroid hormone. The synthesis process depends on vitamin K, C and is regulated by vitamin D3. Part of the synthesized osteocalcin that is not included in the bone matrix is excreted by the kidneys, so its level in the blood depends on the functional state of the kidneys. The level of osteocalcin in the blood can vary depending on the nature of metabolic disorders in the bone and is subject to large daily fluctuations. It is most advisable to determine osteocalcin simultaneously with b-Cross Laps, deoxypyridinoline, in order to determine the rate of bone metabolism (high or low), which will make it possible to select a drug for pathogenetic treatment.
Norms of osteocalcin
Approximately 95% of healthy adults have osteocalcin levels in their blood within the normal range of 11 – 48 ng/ml. But these indicators are typical for adults aged 30 to 50 years.
During the period of intensive growth of children and their puberty, osteocalcin values increase significantly within the range of 77 – 269 ng/ml. And with aging, the values of this protein seriously decrease and range from 14 to 46 ng/ml.
Osteocalcin production follows a circadian rhythm and varies throughout the day, reaching its peak in the early morning and its nadir at midday.()
HORMONAL INFLUENCE OF OSTEOCALCIN ON METABOLISM IN THE BODY (https://www.sciencedirect.com/science/article/pii/S8756328215002355)
Indications for use
1. As an addition to the diagnosis of diseases associated with increased bone turnover: Paget's disease, osteomalacia, osteoporosis, osteosarcoma, metastatic prostate or breast cancer with osteoblastic bone formation, primary hyperparathyroidism, renal osteodystrophy. 2. Monitoring and evaluation of the effectiveness of antiresorptive therapy (including hormone replacement therapy, use of bisphosphonates). 3. In pediatrics, an additional test for diagnosing rickets.
Action and effects of osteocalcin
Osteocalcin helps build strong bones
Osteocalcin is responsible for capturing and binding calcium in bone tissue, which gives bones their strength and flexibility. In order for this process to begin, osteocalcin must first be activated by vitamin K. () For example, mice with low levels of osteocalcin were found to have significantly weaker bones, which even led to bone fractures.()
However, elevated osteocalcin levels are not always a sign of bone strength. In older people, such a high level of this protein is, on the contrary, an indicator of decreased bone density (especially the femoral neck and spine), which can lead to serious fractures. These elevated osteocalcin levels are associated with numerous abnormalities in bone formation.(, , , , )
Osteocalcin regulates insulin and glucose levels
When osteocalcin works as a hormone, it is able to control the balance between insulin and glucose in the body.(And) In the pancreas, this protein increases insulin production by activating the GPRC6A receptors . This increases the production of beta cells in the pancreas, which then begin to produce, store and release more insulin.(, )
Osteocalcin also acts on muscles and other tissues to help maintain glucose levels in balance. It does this by increasing the production of adiponectin in fat cells (adipocytes). Adiponectin, in turn, increases glucose uptake in fat and muscle cells. ()
Low osteocalcin levels can impair the body's ability to use insulin to manage glucose. ()
Osteocalcin stimulates testosterone production
Osteocalcin is associated with male reproductive function. When it acts as a hormone in the blood, it interacts with testicular cells through the GPRC6A receptors. This interaction stimulates an increase in testosterone .()
Blood levels of osteocalcin tend to rise during boys' puberty, while low levels are associated with delayed or delayed puberty. However, since osteocalcin levels can vary greatly from person to person, these levels are not necessarily a reliable marker of pubertal development in an individual.()
Osteocalcin improves muscle strength
Osteocalcin has a direct effect on muscle strength, especially in the arms and legs. Signals in muscle tissue received from osteocalcin help muscles adapt to physical activity. Together, these features help osteocalcin prevent the decline in exercise capacity with age.()
Adequate levels of this protein are known to be positively associated with muscle strength in women aged 70 years and older, reducing the risks of falls and fractures. Higher osteocalcin levels are also associated with increased muscle mass and with the prevention of muscle mass loss with age.()
Osteocalcin improves brain function
Osteocalcin helps increase the production of neurotransmitters - dopamine , norepinephrine , serotonin in the brain (experiments were on mice). These neurotransmitters play an important role in motivation, learning and memory.()
One study looked at 44 people with low osteocalcin levels. All of them were diagnosed with negative changes in the microstructure of the brain (in the hypothalamus, thalamus and subcortical white matter). Such changes can lead to decreased brain efficiency.()
Another study of 117 women aged 71-78 years found that cognitive function improved when osteocalcin levels in the brain increased. Other studies in mice showed impairments in learning and memory when osteocalcin levels decreased.
SCHEME OF RELATIONSHIP BETWEEN CELLS OF BONE TISSUE, VASCULAR SYSTEM, FAT TISSUE AND METABOLISM (https://www.elsevier.es/en-revista-endocrinologia-nutricion-english-edition–412-articulo-cardiovascular-disease-bone-metabolism- S2173509311000080)
Interpretation:
- Primary and secondary hyperparathyroidism, Paget's disease, secondary osteosarcoma, healing period of bone fractures, renal osteodystrophy, chronic renal failure, tumors and bone metastases, diffuse toxic goiter, rapid growth in adolescents
- Hypercortisolism (Itsenko-Cushing disease and syndrome), therapy with glucocorticoid hormones, hypoparathyroidism, primary biliary cirrhosis, pregnancy, somatotropin deficiency, rickets in young children
Sample result (PDF)
High osteocalcin levels
Elevated osteocalcin levels may indicate osteoporosis
Elevated blood levels of osteocalcin have been associated with decreased bone mineral density (low bone mass) and osteoporosis . These findings were obtained in 4 studies with a total of 417 postmenopausal women participants. () Tests to determine the level of osteocalcin in the blood can be used to diagnose and monitor the condition of patients with osteoporosis. This can be done with a routine bone mineral density scan.
Other studies have shown that high levels of osteocalcin in the blood are an indicator of bone loss and, in older people, an indicator of decreased bone density and increased risk of fractures . Animal studies suggest that this is due to bone reabsorption (breakdown of bones resulting from the transfer of minerals into the blood), which is accompanied by increased release of osteocalcin into the blood.()
Vitamin K, vitamin D, and calcium supplements lowered blood osteocalcin levels and increased bone density in a study of 78 postmenopausal women.()
High Osteocalcin Levels Linked to Diabetes in Pregnancy
A study of 130 pregnant women indicated a link between high levels of osteocalcin in the blood and the risk of increased insulin resistance during pregnancy, which can lead to the development of a condition called gestational diabetes (a temporary form of diabetes associated with pregnancy and childbirth).()
Osteocalcin blood levels were higher throughout pregnancy in 48 women with gestational diabetes compared to the other 48 healthy pregnant women.()
Elevated osteocalcin levels are associated with breast density in women
Diagnosed obesity in postmenopausal women, together with increased levels of osteocalcin in the blood, showed a greater likelihood of increased breast density. This increase in breast density represents a significant risk factor for the development of breast cancer . This relationship was found in a study of 239 premenopausal and postmenopausal women aged 40-60 years.()
High osteocalcin levels may indicate anemia
Osteocalcin levels can affect the formation of red blood cells, which carry oxygen in the blood. A study of 939 older men aged 72-79 showed high levels of osteocalcin, which was associated with low red blood cell counts. However, the mechanism of this relationship is not yet known.()
ENDOCRINE ROLE OF OSTEOCALCIN (https://joe.endocrinology-journals.org/content/225/1/R1/F1.expansion.html)
Osteocalcin
Osteocalcin
- a marker of bone tissue metabolism.
It is the main vitamin K-dependent non-collagenous bone matrix protein that binds calcium and hydroxyapatites. It is released by osteoblasts during osteosynthesis and partially enters the bloodstream. Metabolism of osteocalcin
Osteocalcin is produced by osteoblasts and odontoblasts of bone tissue. The bulk of the synthesized protein is part of the extracellular matrix of bone tissue, which is then mineralized to form new bone, and the remainder enters the bloodstream. During bone resorption under the influence of osteoclasts, osteocalcin is released from the bone matrix and enters the blood in the form of non-immune fragments. They are excreted by the kidneys in the form of metabolites of gamma-carboxyglutamic acid (Gla), so the level of osteocalcin in the blood depends on the functional state of the kidneys.
Osteocalcin blood level
The level of osteocalcin in the blood reflects the metabolic activity of osteoblasts of bone tissue, since osteocalcin in the blood is the result of new synthesis, and not its release during bone resorption. The participation of osteocalcin in the regulation of the resorption process is assumed. When osteocalcin levels are high, bone resorption is high. It is an indicator of the level of bone turnover in general and is also a possible prognostic indicator of increased bone disease.
More than 90% of osteocalcin synthesized by osteoblasts in young people and about 70% in adults is included in the bone matrix, and the rest enters the bloodstream. This proportion of TC may vary depending on the nature of metabolic disorders in the bone. OC is removed from the bloodstream by the kidneys (through glomerular filtration and degradation in the renal tubules), so its level in the blood depends on the functional state of the kidneys. The level of OC in the blood is subject to large daily fluctuations.
Limits of detection: 0.5 ng/ml–1500 ng/ml.
Indications:
- diagnosis of osteoporosis;
- monitoring of antiresorptive therapy in patients with osteoporosis;
- hypercalcemic syndrome;
Preparation
It is recommended to donate blood in the morning, between 8 am and 12 pm. Blood is drawn on an empty stomach or after 6–8 hours of fasting. It is allowed to drink water without gas and sugar. On the eve of the examination, food overload should be avoided.
Interpretation of results
Units of measurement: ng/ml.
Increased osteocalcin levels:
- postmenopausal osteoporosis;
- osteomalacia;
- primary and secondary hyperparathyroidism;
- Paget's disease;
- renal osteodystrophy;
- tumors, bone metastases;
- diffuse toxic goiter;
- rapid growth in adolescents;
- chronic renal failure.
Attention!
With a pronounced decrease in glomerular filtration, in particular in chronic renal failure, the level of OC in the blood may be elevated. The presence of OC fragments in the bloodstream due to either its partial destruction in the vascular bed under the influence of circulating proteases, or due to its destruction during bone resorption can also lead to overestimated values when determining OC.
Decreased osteocalcin levels:
- hypercortisolism (Itsenko-Cushing's disease and syndrome);
- glucocorticoid hormone therapy;
- hypoparathyroidism;
- primary biliary cirrhosis;
- pregnancy;
- somatotropin deficiency.